Gene-environment interaction in chronic kidney disease among people with type 2 diabetes from The Malaysian Cohort project: a case-control study.

AIM: To examine the possible gene-environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease. METHODS: A case-control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene-environment interaction analyses. RESULTS: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene-environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person-years (95% CI: 115, 153), with a mean follow-up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene-environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI). CONCLUSIONS: Our findings suggest that the gene-environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease.

Photoprotection awareness and practices among patients with systemic lupus erythematosus and its association with disease activity and severity.

Objective The objective of this paper is to determine photoprotection awareness, knowledge, practices, and its relationship with disease activity and damage in patients with systemic lupus erythematosus (SLE). Methods A cross-sectional study was performed. Data were acquired from in-person interviews and medical records. Results A total of 199 (89.6%) females and 23 (10.4%) males were recruited. Median age was 39.00 (interquartile range (IQR) 18) years, disease duration 12.12 (IQR 8) years, Fitzpatrick skin phototype III 119 (53.6%) and IV 81 (36.5%). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) was 2.95 (IQR 4) while Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-ACR DI) was 1.20 (IQR 2). The majority 205 (92.3%) were aware of sun exposure effects on SLE. Photoprotection methods were shade seeking 209 (94.1%), sun avoidance 212 (95.5%), long pants 168 (75.7%), long sleeves 155 (69.8%), sunscreen 116 (52.3%), sunglasses 114 (51.4%) and head cover 103 (46.4%). Significantly higher photoprotection practice scores (PPS) were observed in females, Malays, and individuals with higher education level and internet accessibility. PPS were not significantly correlated with SLICC-ACR DI and SLEDAI-2 K. Independent predictors for good photoprotection practice (GPP) were ethnicity (OR = 3.66, 95% CI 1.78-7.53), awareness (OR = 3.77, 95% CI 1.09-13.08) and cutaneous involvement (OR = 2.43, 95% CI 1.11-5.28). Photoprotection methods and GPP were not predictors for disease activity or damage. Conclusion Photoprotection awareness and knowledge was good. Shade seeking and sun avoidance were the common photoprotection methods practised. The use of sunscreen requires improvement. Photoprotection awareness and cutaneous manifestation were predictors for GPP. Neither photoprotection methods nor GPP were associated with disease activity or damage.

Serum procalcitonin has negative predictive value for bacterial infection in active systemic lupus erythematosus.

BACKGROUND: Previous studies in systemic lupus erythematosus (SLE) patients have produced conflicting results regarding the diagnostic utility of procalcitonin (PCT). The aim of this study was to determine predictive values of PCT and C-reactive protein (CRP) for bacterial infection in SLE patients. MATERIALS AND METHODS: This was a cross-sectional study of clinic and hospitalized SLE patients with and without bacterial infection recruited over 18 months. Bacterial infection was defined as positive culture results. SLE disease activity was measured using SLEDAI. PCT and CRP were measured by automated immunoassays. RESULTS: Sixty-eight patients (57 females) were studied. Ten patients (15%) had infection. The areas under the receiver operating characteristic curves for PCT and CRP were not significantly different [0.797 (CI 0.614-0.979) versus 0.755 (CI 0.600-0.910)]. In lupus flare patients, PCT but not CRP was higher with infection (p = 0.019 versus 0.195). A PCT of <0.17 ng/ml ruled out infection with 94% negative predictive value (NPV). In remission patients, CRP but not PCT was elevated with infection (p = 0.036 versus 0.103). CRP < 0.57 mg/dl had 96% NPV. CONCLUSION: PCT may be a better marker to rule out bacterial infection in lupus flare but not in remission or general screening.

The effects of angiotensin-converting enzyme gene polymorphism on the progression of immunoglobulin A nephropathy in Malaysian patients.

INTRODUCTION: Angiotensin-converting enzyme (ACE) gene polymorphism, especially the deletion/deletion (DD) genotype, is associated with the disease progression of immunoglobulin A (IgA) nephropathy patients in various studies from both Asia Pacific and European populations. However, recent studies within the same populations were unable to reproduce the same results. Hence, we had studied the distribution of the DD genotype, the association between ACE gene polymorphism and the disease progression, and the factors (other than ACE gene polymorphism) which were involved in the disease progression of our local patients. METHODS: This was a cross-sectional study of biopsy-proven IgA nephropathy patients attending the Nephrology Clinic, Hospital Universiti Kebangsaan Malaysia. Both biochemical and urine tests at the time of first presentation were compared to those at the time of the study, and the disease progression was analysed. The ACE gene polymorphism was identified via PCR-amplification technique, and patients were then categorised into the DD and the non-DD groups for detailed analysis. Histological severity of each renal biopsy was scored according to the predetermined criteria and medications used were recorded. The association between the gene polymorphism and disease progression was then determined. The patients who were stable or had renal function deterioration, were respectively regrouped into Groups 1 and 2, to identity those factors (other than ACE gene polymorphism), which were involved in the disease progression. RESULTS: 60 patients with adequate renal histopathological examination were recruited. Their mean age was 40.9 +/- 12.3 years and the follow-up duration was 4 +/- 3 years (range 6 months-20 years). More than two-thirds of them were treated with ACE inhibitors or angiotensin receptor blockers and 8.3 percent received the combination treatment. The DD genotype was noted in 13.3 percent of study patients, insertion/insertion in 48.3 percent and insertion/deletion genotype in 38.3 percent. Although the estimated glomerular filtration rate (eGFR) of both groups were the same during their initial presentation, the DD patients had more severe disease compared to the non-DD patients at the time of the study. Their serum creatinine and eGFR was 178 (IQR 31.3) micromol/L and 42.1 +/- 31.1 ml/min/1.73 square metres, whereas the non-DD patients had serum creatinine and eGFR of 79 (IQR: 88.3) micromol/L and 76.6 +/- 42.1 ml/min/1.73 square metres, respectively (p-value is less than 0.01). The DD patients were also found to have more severe vascular damage in their renal biopsies compared to the non-DD patients. The annual rate of decline in eGFR was not significantly different between the two groups. It was -5.7 +/- 2.2 ml/min/1.73 square metres/year for the DD group and -4.8 +/- 2.0 ml/min/1.73 square metres/year for the non-DD group (p-value is equal to 0.5). They also had severe proteinuria with UPCI of 0.09 (IQR 0.2) g/mmol creatinine vs. 0.04 (IQR 0.10) g/mmol creatinine (p-value is less than 0.01). The study also confirmed that patients who had higher systolic blood pressure, greater proteinuria and longer follow-up duration had significant renal function deterioration compared to those who did not. CONCLUSION: The DD genotype, although found in a minority of the patients, might have adversely affected the disease progression of our IgA nephropathy patients. Higher systolic blood pressure, greater proteinuria and longer follow-up duration were the other prognostic factors in IgA nephropathy patients. However, appropriate treatment, especially prompt use of renin-angiotensin-aldosterone system blockade, should stabilise the disease regardless of their genotype.