The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia.

Pre-eclampsia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-eclampsia. The association of INSR rs2059806 with pre-eclampsia was tested in two cohorts - a Caucasian case control group (123 pre-eclamptic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-eclampsia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-eclamptic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-eclamptic women who delivered small for gestational age infants compared with the uncomplicated pregnancies (10.8% versus 4.2%, OR[95%CI] = 2.8[1.0-7.4], P = 0.03). Thus, it was found that the INSR rs2059806 SNP is also associated with pre-eclampsia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-eclampsia and subsequent vascular and metabolic diseases.

The obesity-related FTO gene variant associates with the risk of recurrent miscarriage.

OBJECTIVE: To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. DESIGN: Candidate gene association study. SETTING: Human Genetics Unit, Colombo, Sri Lanka. POPULATION: A total of 202 Sinhalese women with two or more first-trimester miscarriages and no living children (cases) and 202 age- and ethnicity-matched women with no history of miscarriage and having two or more living children (controls). METHODS: Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. MAIN OUTCOME MEASURES: The prevalence of the single nucleotide polymorphism in cases and controls. RESULTS: The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. CONCLUSION: The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.

Microbiome of the placenta in pre-eclampsia supports the role of bacteria in the multifactorial cause of pre-eclampsia.

AIM: This study was aimed at detecting, identifying, quantifying and comparing the bacteria present in the placental tissues of women with pre-eclampsia with that of normotensive pregnant women. MATERIAL AND METHODS: Placental tissue samples were collected from 55 primiparous women with pre-eclampsia (cases) and 55 matched primiparous normotensive pregnant women (controls) at the time of delivery by cesarean section. Genotyping was carried out in two stages. First the samples were screened for the presence of bacteria by polymerase chain reaction (PCR) for the 16S rRNA gene. Next, the samples that were PCR-positive for the 16S rRNA gene were screened by next-generation sequencing on an Illumina MiSeq platform. RESULTS: Seven (12.7%) placental tissue samples from women with pre-eclampsia were PCR-positive. All the placental samples from control women were negative (P = 0.006). The complete microbiome of the seven samples was revealed through next-generation sequencing. The organisms that were present included Bacillus cereus, Listeria, Salmonella, Escherichia (all of which are usually associated with gastrointestinal infection); Klebsiella pneumonia and Anoxybacillus (both of which are usually associated with respiratory tract infections); and Variovorax, Prevotella, Porphyromonas, and Dialister (all of which are usually associated with periodontitis). CONCLUSIONS: This study confirms the presence of bacteria in the placental tissues of a subset of women with pre-eclampsia and supports the role of bacteria in the multifactorial cause of pre-eclampsia.

Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion.

Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children; controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.

Polymorphism in the epidermal growth factor gene is associated with pre-eclampsia and low birthweight.

AIM: We have previously reported that polymorphism in the epidermal growth factor (EGF) gene is associated with pre-eclampsia and birthweight based on case-control association studies involving two single nucleotide polymorphisms (SNP). We extended that work to investigate other SNP in the EGF gene for their association with pre-eclampsia and the weight of babies at birth. MATERIAL AND METHODS: A population-based DNA collection was genotyped to determine whether the selected SNP were polymorphic in the study population. In total, 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for the polymorphic SNP using polymerase chain reaction/restriction fragment length polymorphism and MassARRAY Sequenom iPLEX methodology. RESULTS: The rs3756261A, rs4444903G, rs2237051G haplotype was associated with the highest increased risk of pre-eclampsia (odds ratio: 3.70, 95% confidence interval: 1.38-9.94; P = 0.016). The rs3756261A allele was the one that contributed to this high degree of significance. The same allele was present in the haplotype rs3756261A, rs11568943G, rs2237051G, rs11569017A, rs4698803T (likelihood ratio statistic = 20.4671, d.f. = 3, P-value = 0.0001), which was associated with the lower birthweight. CONCLUSIONS: In this study we found further evidence for the association of polymorphism in the EGF gene with pre-eclampsia and the weight of babies at birth and identified rs3756261A>G as the SNP that makes the most significant contribution to this association. Bioinformatic analysis showed that this effect may be mediated by caudal type homeohox-2, a transcriptional repressor expressed in the trophoblast, for which a binding site is created at this polymorphic site when the rs3756261A allele is present.

Clinical and genetic features of Huntington disease in Sri Lanka.

BACKGROUND: Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. METHODS: Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. RESULTS: Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (<20 years) and 3 with late onset (>60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p < 0.05). Twenty two (62.8%) had a positive family history, with 13/22 (59.1%) showing a paternal inheritance of the disease. In both groups, those with a family history had a significantly lower age of presentation (p < 0.05). The mean CAG repeat length in patients with FP alleles was 44.6 ± 5 and RP alleles was 37.2 ± 1.1. Age of onset and CAG repeat length of the HTT gene showed significant inverse correlation (p < 0.0005, R2 = 0.727). CONCLUSIONS: The clinical and genetic features seen in patients with Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.

Autosomal dominant hereditary ataxia in Sri Lanka.

BACKGROUND: Spinocerebellar ataxias (SCA) are a group of hereditary neurodegenerative disorders. Prevalence of SCA subtypes differ worldwide. Autosomal dominant ataxias are the commonest types of inherited ataxias seen in Sri Lanka. The aim of the study is to determine the genetic etiology of patients with autosomal dominant ataxia in Sri Lanka and to describe the clinical features of each genetic subtype. METHODS: Thirty four patients with autosomal dominant ataxia were recruited. For every patient the following was done: recording of clinical details and genotyping for SCA 1, 2, 3, 6, 7, 8, 12, and 17. RESULTS: Sixty one per cent of the subjects were identified as SCA1. One subject had SCA2, 12 remain unidentified. Mean age at onset was 34.8 ± 10years for SCA1 and 32.7 ± 9.8 for non SCA1. 76% of SCA1 patients and 50% of non SCA1 were using walking aids. Quantification of symptoms and signs were similar in the SCA1 and non SCA1 groups. Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients. Mean CAG repeat length in SCA1 patients was 52.0 ± 3.8, with greater anticipation seen with paternal inheritance. CONCLUSION: SCA1 was the predominant subtype and showed similar phenotype to previous reports. However, disease severity was higher and depression more prevalent in this population than previously described.

Prevalence of chromosomal abnormalities in Sri Lankan women with primary amenorrhea.

AIM: Chromosomal abnormalities are implicated in the etiology of primary amenorrhea. The underlying chromosomal aberrations are varied and regional differences have been reported. The objective of this study is to describe the prevalence of various types of chromosomal abnormalities in Sri Lankan women with primary amenorrhea. MATERIAL AND METHODS: Medical records of all patients diagnosed with primary amenorrhea referred for cytogenetic analysis to two genetic centers in Sri Lanka from January 2005 to December 2011 were reviewed. Chromosome culture and karyotyping was performed on peripheral blood samples obtained from each patient. Data were analyzed using standard descriptive statistics. RESULTS: Altogether 338 patients with primary amenorrhea were karyotyped and mean age at testing was 20.5 years. Numerical and structural chromosomal abnormalities were noted in 115 (34.0%) patients which included 45,X Turner syndrome (10.7%), Turner syndrome variants (13.9%), XY females (6.5%), 45,X/46,XY (0.9%), 46,XX/46,XY (0.6%), 47,XXX (0.3%), 47,XX,+ mar (0.3%), 46,X,i(X)(p10) (0.3%), 46,XX with SRY gene translocation on X chromosome (0.3%) and 46,XX,inv(7)(p10;q11.2) (0.3%). Short stature, absent secondary sexual characteristics, neck webbing, cubitus valgus and broad chest with widely spaced nipples were commonly seen in patients with Turner syndrome and variant forms. Neck webbing and absent secondary sexual characteristics were significantly associated with classical Turner syndrome than variant forms. CONCLUSION: A considerable proportion of women with primary amenorrhea had chromosomal abnormalities. Mean age at testing was late suggesting delay in referral for karyotyping. Early referral for cytogenetic evaluation is recommended for the identification of underlying chromosomal aberrations in women with primary amenorrhea.

Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia.

AIM: Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case-control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka. MATERIALS AND METHODS: A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects. CONCLUSIONS: These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a.

Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

AIM: Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. MATERIAL AND METHODS: Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. RESULTS: The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. CONCLUSIONS: The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women.

The low frequency of Y chromosome microdeletions in subfertile males in a Sinhalese population of Sri Lanka.

AIMS: This study was designed to determine the prevalence of azoospermia factor (AZF) microdeletions on the Y chromosome in Sri Lankan Sinhalese infertile men with azoospermia and severe oligozoospermia. SETTINGS AND DESIGN: The patient group was 207 karyotypically normal infertile Sinhalese males. MATERIALS AND METHODS: The presence of 13 sequence-tagged site (STS) markers in the AZF region was tested using multiplex polymerase chain reaction (M-PCR). One hundred and twenty unselected men were also studied as a control group. RESULTS: Three (1.5%) had classic Y chromosome microdeletions in the AZFc sub-region. CONCLUSIONS: These results suggest a much lower Y chromosome microdeletion frequency than previously thought, even among a strictly selected group of sub-fertile males in Sri Lanka.

A child with mosaicism for deletion (14)(q11.2q13).

In this case report we describe a child with a de novo deletion in the (q11.2q13) region of chromosome 14. The child presented with dysmorphic features - anophthalmia, microcephaly, and growth retardation. Cytogenetic studies showed mosaicism. The karyotype was 46,XX,del(14)(q11.2;q13) [16] /46,XX [9]. We compared the features observed in this child with that of others with the same deletion reported in scientific literature and found that this is the first report of a child mosaic for this deletion. It is also the first time it has been reported in association with anophthalmia.

Y chromosome microdeletions are not associated with spontaneous recurrent pregnancy loss in a Sinhalese population in Sri Lanka.

BACKGROUND: Many advances have been made in reproductive medicine, yet the spontaneous loss of a pregnancy remains the most common complication of pregnancy. The aetiology of spontaneous recurrent pregnancy loss (RPL) is multifactorial. Y chromosome microdeletions are found in ∼7% of men with low sperm counts and, compared with the general population, a higher frequency of spontaneous pregnancy loss occurs in infertile couples. The current study was designed to examine whether Y chromosome microdeletions were associated with RPL in a Sinhalese population in Sri Lanka. METHODS: The subjects were 76 male partners of couples where the female partner had experienced three or more RPLs. One hundred and twenty random males from the general population were also analysed as a control group. DNA extracted from peripheral blood was tested for Y chromosome microdeletions in the azoospermic factor (AZF), AZFa, AZFb, AZFc regions using a multiplex PCR amplification system. Partial deletions within the AZFc region were also tested. RESULTS: None of the men (76 with RPL, and the 120 controls) had any microdeletions in the AZFa, AZFb, AZFc regions or partial deletions in the AZFc region. CONCLUSIONS: Y chromosome microdeletions do not appear to be important in the aetiology of RPL in this population in Sri Lanka.

A Sri Lankan child with 49,XXXXY syndrome.

Pentasomy 49,XXXXY is a rare sex chromosome disorder usually presenting with ambigous genitalia, facial dysmorphism, mental retardation and a combination of cardiac, skeletal and other malformations. The incidence of the condition is estimated to be 1 in 85,000 male births. Previously, this condition was identified as a Klinefelter variant. The condition is suspected in a patient, by a combination of characteristic clinical findings, and the diagnosis is confirmed by chromosome culture and karyotyping. In the case we report here, the main presentation of ambiguous genitalia led to a suspicion of a sex chromosome aneuploidy which was subsequently confirmed by chromosomal analysis.

Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population--implications for association study design and clinical genetic testing services.

We investigated the prevalence of genotypes/alleles of single nucleotide polymorphisms (SNP) and haplotypes defined by them in three genes in which variations are associated with venous thromboembolism in 80 Sinhalese, 80 Sri Lankan Tamils and 80 Moors in the Sri Lankan population and compared the SNP data with that of other populations in Southern India and haplotype data with that of HapMap populations. The genes and polymorphisms investigated were Methylenetetrahydrofolate reductase (MTHFR) - 677C>T (rs1801133), 1298A>C (rs1801131), 1317T>C, 1793G>A (rs2274976); Factor V (F5) - 1691G>A (rs6025) and 4070A>G (rs1800595); and prothrombin (F2) - 20210G>A (rs1799963). The polymorphisms were genotyped using PCR/RFLP methods. The prevalence of the variant alleles of each polymorphism in the Sinhalese, Tamils, and Moors was MTHFR 677T: Sinhalese - 13%, Tamils - 9%, Moors - 9%. 1317T>C: Sinhalese - 0%; Tamils - 0%; Moors - 0%. 1793A: Sinhalese - 19%, Tamils - 19%, Moors - 19%. F5 1691A: Sinhalese - 2%, Tamils - 3%, Moors - 2%. 4070G: Sinhalese - 6%, Tamils - 5%, Moors - 8%. F2 20210A: Sinhalese - 0%, Tamils - 0%, Moors - 0%. The frequencies observed were similar to data from other South Indian populations; the haplotype data showed haplotypes unique to the Sri Lankan population when compared to HapMap populations. rs9651118 was identified as a SNP that splits the haplotypes harbouring the functionally significant 677T allele in the MTHFR gene. This data would be useful in planning genetic association studies in the Sri Lankan population and in deciding on which genetic variants should be tested in a clinical genetic testing service.

Genetic associations of inflammatory bowel disease in a South Asian population.

AIM: To estimate prevalence and phenotypic associations of selected inflammatory bowel disease (IBD)-associated genetic variants among Sri Lankan patients. METHODS: A case study of histologically confirmed ulcerative colitis (UC) or Crohn's disease (CD) patients with ≥ 1 year disease duration, who were compared to unrelated, gender-matched, healthy individuals as controls, was conducted at four major centers in Sri Lanka. Phenotypic data of the cases were obtained and all participants were genotyped for 16 selected genetic variants: IL12B:rs1045431, IL23R:rs11805303, ARPC2:rs12612347, IRGM:rs13361189, IL26/IL22:rs1558744, CDH1:rs1728785, IL10:rs3024505, FCGR2A:rs3737240, PTGER4:rs4613763, IL17REL/PIM3:rs5771069, HNF4a:rs6017342, STAT3:rs744166, SMURF1:rs7809799, LAMB1:rs886774, HLA-DRB5, DQA1, DRB1, DRA:rs9268853, MST1, UBA7, and APEH:rs9822268. The genotypes of all variants were in Hardy-Weinberg Equilibrium (P > 10-3). To account for multiple hypothesis testing, P-values < 0.003 were considered significant. RESULTS: A total of 415 patients and 465 controls were recruited. Out of the single nucleotide polymorphisms (SNPs) tested, the majority were not associated with IBD in Sri Lankans. Significant positive associations were noted between rs886774 (LAMB1-gene) and UC (odds ratio (OR) = 1.42, P = 0.001). UC patients with rs886774 had mild disease (OR = 1.66, P < 0.001) and remained in remission (OR = 1.48, P < 0.001). A positive association was noted between rs10045431 (IL 12B gene) and upper gastrointestinal involvement in CD (OR = 4.76, P = 0.002). CONCLUSION: This confirms the heterogeneity of allelic mutations in South Asians compared to Caucasians. Most SNPs and disease associations reported here have not been described in South Asians.

Polymorphisms in the inflammatory pathway genes and the risk of preeclampsia in Sinhalese women.

OBJECTIVE: Elevated pro-inflammatory cytokines play an important role in the pathogenesis of preeclampsia. We investigated the prevalence of functional polymorphisms in genes regulating inflammation in preeclamptic women. METHODS: One hundred seventy-five nulliparous Sinhalese women with preeclampsia (cases) and 171 normotensive women matched for age, ethnicity, parity and body mass index (BMI) (controls) were recruited. Preeclampsia was diagnosed using international guidelines. Genotyping was performed on DNA extracted from peripheral blood using the Sequenom MassARRAY system. RESULTS: The prevalence of the CT genotype of IL1A rs17561 polymorphism was increased in preeclamptic women compared with controls {p = 0.04, odds ratio (OR) [95% class interval (CI)] = 1.6 (1.0-2.5)}. The prevalence of the CT genotype [p = 0.01, OR (95% CI) = 1.8 (1.1-2.8)] and the dominant model (CT + TT) [p = 0.03, OR (95% CI) = 1.6 (1.1-2.5)] of the IL1A rs1800587 polymorphism were increased in preeclamptic women compared with controls. The prevalence of the GA genotype [p = 0.04, OR (95% CI) = 0.6 (0.4-0.9)] and the dominant model (GA + AA) [p = 0.03, OR (95% CI) = 0.6 (0.4-0.9)] of the MBL1 rs1800450 polymorphism were reduced in preeclamptic women compared to controls. CONCLUSION: Genotypes conferring a pro-inflammatory phenotype are increased in preeclamptic women.